Activation of Mineralocorticoid Receptors by Exogenous Glucocorticoids and the Development of Cardiovascular Inflammatory Responses in Adrenalectomized Rats

摘要

Foxo1-dependent expression of orexigenic neuropeptide Agouti-related peptide and cessation of feeding. Mitotane therapy is associated with many side effects, including thyroid function perturbations mimicking central hypothyroidism, possibly due to laboratory test interference or pituitary direct effects of mitotane. We investigated whether increasing concentrations of mitotane in the therapeutic range might interfere with thyroid hormone assays and evaluated the effects of mitotane on a mouse TSH-producing pituitary cell line. TSH, free T4, and free T3 levels do not significantly change in sera from hypo-, hyper-, or euthyroid patients after addition of mitotane at concentrations in the therapeutic window. In the mouse TaT1 cell line, mitotane inhibits both TSH expression and secretion, blocks TSH response to TRH, and reduces cell viability, inducing apoptosis at concentrations in the therapeutic window. TRH is not capable of rescuing TaT1 cells from the inhibitory effects of mitotane on TSH expression and secretion, which appear after short time treatment and persist over time. Our results demonstrate that mitotane does not interfere with thyroid hormone laboratory tests but directly reduces both secretory activity and cell viability on pituitary TSH-secreting mouse cells. These data represent a possible explanation of the biochemical picture consistent with central hypothyroidism in patients undergoing mitotane therapy and.